Mineralocorticoid receptor

1Y9R, 1YA3, 2A3I, 2AA2, 2AA5, 2AA6, 2AA7, 2AAX, 2AB2, 2ABI, 2OAX, 3VHU, 3VHV, 3WFF, 3WFG, 4PF3, 4TNT, 4UDB, 4UDA, 5HCV4306110784ENSG00000151623ENSMUSG00000031618P08235Q8VII8NM_000901NM_001166104NM_001354819NM_001083906NP_000892NP_001159576NP_001341748n/aThe mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.1gdc: REFINED SOLUTION STRUCTURE OF THE GLUCOCORTICOID RECEPTOR DNA-BINDING DOMAIN1rgd: STRUCTURE REFINEMENT OF THE GLUCOCORTICOID RECEPTOR-DNA BINDING DOMAIN FROM NMR DATA BY RELAXATION MATRIX CALCULATIONS1y9r: Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to deoxycorticosterone and harboring the S810L mutation responsible for a severe form of hypertension1ya3: Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to progesterone and harboring the S810L mutation responsible for a severe form of hypertension2a3i: Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor2aa2: Mineralocorticoid Receptor with Bound Aldosterone2aa5: Mineralocorticoid Receptor with Bound Progesterone2aa6: Mineralocorticoid Receptor S810L Mutant with Bound Progesterone2aa7: Mineralocorticoid Receptor with Bound Deoxycorticosterone2aax: Mineralocorticoid Receptor Double Mutant with Bound Cortisone2ab2: Mineralocorticoid Receptor Double Mutant with Bound Spironolactone2abi: Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to deoxycorticosterone2gda: REFINED SOLUTION STRUCTURE OF THE GLUCOCORTICOID RECEPTOR DNA-BINDING DOMAIN The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2. MR is a receptor with equal affinity for mineralocorticoids and glucocorticoids. It belongs to the nuclear receptor family where the ligand diffuses into cells, interacts with the receptor and results in a signal transduction affecting specific gene expression in the nucleus. MR is expressed in many tissues, such as the kidney, colon, heart, central nervous system (hippocampus), brown adipose tissue and sweat glands. In epithelial tissues, its activation leads to the expression of proteins regulating ionic and water transports (mainly the epithelial sodium channel or ENaC, Na+/K+ pump, serum and glucocorticoid induced kinase or SGK1) resulting in the reabsorption of sodium, and as a consequence an increase in extracellular volume, increase in blood pressure, and an excretion of potassium to maintain a normal salt concentration in the body. The receptor is activated by mineralocorticoids such as aldosterone and its precursor deoxycorticosterone as well as glucocorticoids, like cortisol. In intact animals, the mineralocorticoid receptor is 'protected' from glucocorticoids by co-localization of an enzyme, corticosteroid 11-beta-dehydrogenase isozyme 2 (a.k.a. 11β-hydroxysteroid dehydrogenase 2; 11β-HSD2), that converts cortisol to inactive cortisone. It also responds to some progestins. Spironolactone and eplerenone are steroidal MR antagonists of the spirolactone group. Activation of the mineralocorticoid receptor, upon the binding of its ligand aldosterone, results in its translocation to the cell nucleus, homodimerization and binding to hormone response elements present in the promoter of some genes. This results in the complex recruitment of the transcriptional machinery and the transcription into mRNA of the DNA sequence of the activated genes. An activating mutation in the NR3C2 gene (S810L) results in constitutive activity of the mineralocorticoid receptor, leading to severe early-onset hypertension that is exacerbated by pregnancy. In a family known to harbor the S810L mutation, 3 individuals carrying the mutation died of chronic heart failure before age 50. Additional studies have shown that this activated version of MR can positively respond to ligands that are traditionally antagonists, such as endogenous hormones like progesterone, and the diuretic drugs spironolactone and eplerenone. Currently, the non-steroidal anti-mineralocorticoid drug Finerenone (Bayer) is in phase III clinical trials for the treatment of chronic heart failure. Mineralocorticoid receptor has been shown to interact with: